This proposal will examine some of the potential determinants of perinatal transmission of HIV. Recently it was shown that the susceptibility of CD4+ T cells to HIV infection is related to both the quantity of b chemokine (MIP-1a, MIP-1 b and RANTES) produced by their CD4+ T cells and to the expression of the b chemokine receptor 5 (CCR5). This receptor was recently identified as the co-receptor for monocytotropic (M-tropic) isolates of HIV, which are the viruses that are mainly transmitted heterosexually and perinatally. Individuals who have homozygous mutations of the CCR5 receptor are resistant to HIV infection with M-tropic isolates. We will examine whether there is a correlation between either CCR5 expression or chemokine production and perinatal HIV transmission. As these chemokines also mediate CD8+ T- cell-mediated HIV suppression, which we have identified as an important early protective immune response in HIV-infected infants, we will also measure CD8 viral suppressive activity (CD8-VSA) to try to assess whether it also plays a role in perinatal HIV transmission. The laboratory will be used for oligonucleotide synthesis, ELISA, PCR, and recombinant DNA techniques. FACS analysis of CCR5 expression and cell isolation, culture and infections will be performed in the Pediatric Infectious Diseases Laboratory.